This STTR proposal describes collaborative research between Zdye LLC and Montana State University (MSU) to synthesize and demonstrate innovative ultrasensitive, fluorescent dyes for multicolor (multiplex) detection in proteomics. The resulting "Zdyes" are designed for vastly improved quantitation of differential protein expression and changes in protein post-translational modifications. Proteomics is a major frontier in biotechnology as proteins do most of the work in cells and protein activity is largely controlled by posttranslational modifications. While proteomics has enormous potential for revealing biological mechanisms, current methods fall short of fulfilling this promise. Zdyes will provide at least a hundred fold sensitivity increase over current technology for detection on 2D gels. Phase I will establish Zdye feasibility to improve recovery for enhanced identification of proteins and protein modifications by mass spectrometry, and for quantitative protein expression ratios with three-color channels. Phase II will carry out beta testing, and incorporate additional dye color channels to simultaneously monitor protein post-translational modifications. The Zdye/MSU research team has extensive relevant expertise and Zdye is prepared to produce and commercialize the resulting products. Zdyes will have immediate positive impact on diagnostic development and research in virtually all health fields, including preventative medicine, type 2 diabetes, heart disease and cancer.